Mapping monoaminergic neurons with [3H] reserpine by autoradiography

The synthesis of [3H] reserpine of high specific activity is described. The accumulation of radioactivity in peripheral sympathetically innervated organs and in the brain after intravenous injection of [3H] reserpine to rats was measured biochemically and its localization studied by light-microscopic autoradiography. In most of the organs and tissues investigated minute quantities of [3H] reserpine persisted up to 10 days after injection. By autoradiography, it was observed that silver grains were unevenly distributed in various brain regions and peripheral organs 18 h and up to 10 days after administration of [3H] reserpine. Pretreating (but not post-treating) animals with non-radioactive reserpine prevented by up to 80% the accumulation of radiolabel and abolished to a great extent the autoradiographic localization. The fact that the persistently bound radiolabel is confined to monoaminergic neurons suggests that it is irreversibly bound to its target site, the amine-storing vesicle. Support for this interpretation comes from studies demonstrating a fast anterograde axonal transport of [3H] reserpine in the nigrostriatal tract after intranigral injection of the radiolabel. These findings demonstrate that [3H] reserpine of high specific activity is a useful tool in studies designed to map monoaminergic pathways in the brain and to further characterize amine-storing mechanisms. (author)